Support is requested for the 2006 and 2007 Gordon Research Conferences on Enzymes, Coenzymes and Metabolic Pathways, which are slated to be held July 16-21, 2006 and July 15-20, 2007 at the University of New England in Biddeford, Maine. Underlying the biological processes of every successful living organism is a vast network of biochemical pathways that occur in a highly ordered fashion. Key to this order is the regulated activity of an equally vast network of unique macromolecular catalysts - the enzymes and ribozymes and their associated cofactors and coenzymes that provide the templates for specific reactants to pass through low energy paths to yield specific products. While the flux through any particular reaction will be dependent on the inherent activity of the catalyst and a variety of direct and indirect regulatory processes, the fidelity of each reaction is entirely dependent on the integrity of the macromolecular catalyst itself. Defects in the catalyst that alter its ability to be regulated, abolish its activity or alter its catalytic mechanism to allow production of side products can be highly detrimental to the organism. The key to understanding these defects, i.e., what can go wrong, is an understanding of how it works in the first place, i.e., of the mechanism of the catalyzed reaction and the intricacies of how the structural features of the macromolecule contribute to and regulate the catalytic mechanism. Elucidation and discussion of these mechanisms is the fundamental theme of the .Enzymes, Coenzymes and Metabolic Pathways Gordon Conference. The 2006 program will focus on mechanisms of enzyme action in a broad variety of biological contexts. Speaker and discussant selection for the 2006 meeting is complete and the program is described. Topics include: enzymes in complex systems, understanding and targeting enzymes in disease, novel mechanisms of metal ion and cofactor catalysis, catalysis by enzymes at membrane surfaces, catalysis involving nucleic acids as substrates and as catalysts, novel mechanisms of enzyme catalysis and regulation, and frontiers of enzyme mechanisms. A diverse group of both established and younger investigators have been invited from academia, industry and research institutes to participate as speakers and discussion leaders. Women and minorities comprise more than a third of the invitees and the co-Chairs will strive to attain a similar diversity in selecting attendees for the meetings. [unreadable] [unreadable] [unreadable]